Elsevier

Experimental Eye Research

Volume 88, Issue 4, 30 April 2009, Pages 799-807
Experimental Eye Research

Review
Biomechanics of the optic nerve head

https://doi.org/10.1016/j.exer.2009.02.003Get rights and content

Abstract

Biomechanical factors acting at the level of the lamina cribrosa (LC) are postulated to play a role in retinal ganglion cell dysfunction and loss in glaucoma. In support of this postulate, we now know that a number of cell types (including lamina cribrosa cells) are mechanosensitive. Here we briefly review data indicating cellular stretching, rate of stretching and substrate stiffness may be important mechanosensitivity factors in glaucoma. We then describe how experiments and finite element modeling can be used to quantify the biomechanical environment within the LC, and how this environment depends on IOP. Generic and individual-specific models both suggest that peripapillary scleral properties have a strong influence on LC biomechanics, which can be explained by the observation that scleral deformation drives much of the IOP-dependent straining of the LC. Elegant reconstructions of the LC in monkey eyes have shown that local strains experienced by LC cells depend strongly on laminar beam microarchitecture, which can lead to large local strain elevations. Further modeling, suitably informed by experiments, is needed to better understand lamina cribrosa biomechanics and how they may be involved in glaucomatous optic neuropathy.

Section snippets

Ocular biomechanics in glaucoma

Elevated intraocular pressure (IOP) remains the primary risk factor for development of glaucomatous optic neuropathy (Lesk et al., 2003, Bengtsson and Heijl, 2005, Heijl et al., 2002), and consistent, sustained and significant reduction of IOP slows or eliminates visual field loss in glaucuma (AGISInvestigators, 2000, Anderson et al., 2001, Heijl et al., 2002, Lesk et al., 2003). IOP is, by definition, a mechanical entity – the normal force per unit area exerted by the intraocular fluids on the

Cellular mechanobiology

Cells are sensitive to many stimuli, including mechanical stimuli. Before describing some of the evidence supporting mechanical factors as important influences on cellular behavior, it is worth introducing some terms from biomechanics.

Strain is the change in length of a tissue element divided by its initial length (Humphrey, 2002, Ethier and Simmons, 2007), and is thus a measure of the local tissue deformation, usually expressed as a percentage. As it deforms, a material can undergo tension,

Quantifying lamina cribrosa biomechanics

Based on the above, as well as the possibility that mechanical forces may lead to direct failure (tearing) of connective tissue fibers in the ONH (Burgoyne et al., 2005), it seems important to understand the biomechanical environment within the LC. Unfortunately, it is difficult to make measurements on the LC directly because it is small, fragile and relatively inaccessible.

Some researchers have studied the movement of the vitreoretinal surface of the ONH as a surrogate for LC motion (Zeimer

The influence of the sclera

A somewhat surprising outcome of the above models is the suggestion that the properties of the sclera have a stronger-than-expected influence on the biomechanics of the ONH. Soft tissues, such as the sclera, often exhibit complex mechanical responses to loading, which may be necessary for the proper description of the effects of IOP on the ONH (Fung, 1993). This motivates studies designed to characterize the biomechanical properties of the sclera, particularly of the peripapillary sclera. The

The influence of retrolaminar tissue pressure

When considering LC biomechanics it is natural to focus on the role of IOP, since it is clinically observable and clearly important. However, from a biomechanical viewpoint, we should remind ourselves that it is the difference between IOP and retrolaminar tissue pressure (RLTp) that directly loads the LC. Put another way, if this pressure difference were zero, then the LC would experience zero net direct loading. Note however this does not mean that the lamina would be free of all biomechanical

Conclusions

The biomechanics of the LC are complex and potentially important in glaucomatous optic neuropathy. The stiffness and thickness of the peripapillary sclera and the microarchitecture of the laminar beams both have a strong effect in the mechanical insult experienced by cells in the LC. Studies in which numerical modeling is informed by experiments offer a powerful way to better understand LC biomechanics. Such characterization of the biomechanical environment within the LC must in turn be coupled

References (89)

  • J.D. Pena et al.

    Elastosis of the lamina cribrosa in glaucomatous optic neuropathy

    Exp. Eye Res.

    (1998)
  • J.T. Siegwart et al.

    Regulation of the mechanical properties of tree shrew sclera by the visual environment

    Vision Res.

    (1999)
  • I.A. Sigal et al.

    Predicted extension, compression and shearing of optic nerve head tissues

    Exp. Eye Res.

    (2007)
  • S.L. Woo et al.

    Nonlinear material properties of intact cornea and sclera

    Exp. Eye Res.

    (1972)
  • AGISInvestigators

    The Advanced Glaucoma Intervention Study (AGIS): 7. The relationship between control of intraocular pressure and visual field deterioration. The AGIS Investigators

    Am. J. Ophthalmol.

    (2000)
  • D.R. Anderson et al.

    Natural history of normal-tension glaucoma

    Ophthalmology

    (2001)
  • D.R. Anderson et al.

    Effect of intraocular pressure on rapid axoplasmic transport in monkey optic nerve

    Invest. Ophthalmol.

    (1974)
  • J.L. Battaglioli et al.

    Measurements of the compressive properties of scleral tissue

    Invest. Ophthalmol. Vis. Sci.

    (1984)
  • A.J. Bellezza et al.

    The optic nerve head as a biomechanical structure: initial finite element modeling

    Invest. Ophthalmol. Vis. Sci.

    (2000)
  • B. Bengtsson et al.

    A long-term prospective study of risk factors for glaucomatous visual field loss in patients with ocular hypertension

    J. Glaucoma

    (2005)
  • D.J. Brown et al.

    Application of second harmonic imaging microscopy to assess structural changes in optic nerve head structure ex vivo

    J. Biomed. Opt.

    (2007)
  • J.A. Buckwalter et al.

    Perspectives on chondrocyte mechanobiology and osteoarthritis

    Biorheology

    (2006)
  • C.F. Burgoyne et al.

    Three-dimensional reconstruction of normal and early glaucoma monkey optic nerve head connective tissues

    Invest. Ophthalmol. Vis. Sci.

    (2004)
  • C.F. Burgoyne et al.

    Posterior Bowing of the Lamina Cribrosa and Peripapillary Sclera are Clinically Detectable Within Heidelberg Spectralis 3D OCT Volumes of Non-human Primate (NHP) Optic Nerve Head (ONH) Following Acute and Chronic IOP Elevation. Program#/Poster # 3655/D1046

    (2008)
  • C.F. Dewey et al.

    The dynamic response of vascular endothelial cells to fluid shear stress

    J. Biomech. Eng.

    (1981)
  • Downs, J., Roberts, M.D., Burgoyne, C.F., Hart, R.T., 2007b. Finite element modeling of the lamina cribrosa...
  • J.C. Downs et al.

    Peripapillary scleral thickness in perfusion-fixed normal monkey eyes

    Invest. Ophthalmol. Vis. Sci.

    (2002)
  • J.C. Downs et al.

    Viscoelastic characterization of peripapillary sclera: material properties by quadrant in rabbit and monkey eyes

    J. Biomech. Eng.

    (2003)
  • J.C. Downs et al.

    Viscoelastic material properties of the peripapillary sclera in normal and early-glaucoma monkey eyes

    Invest. Ophthalmol. Vis. Sci.

    (2005)
  • J.C. Downs et al.

    Three-dimensional histomorphometry of the normal and early glaucomatous monkey optic nerve head: neural canal and subarachnoid space architecture

    Invest. Ophthalmol. Vis. Sci.

    (2007)
  • M.E. Edwards et al.

    Use of a mathematical model to estimate stress and strain during elevated pressure induced lamina cribrosa deformation

    Curr. Eye Res.

    (2001)
  • M.E. Edwards et al.

    Role of viscoelastic properties of differentiated SH-SY5Y human neuroblastoma cells in cyclic shear stress injury

    Biotechnol. Prog.

    (2001)
  • C.R. Ethier et al.

    Ocular biomechanics and biotransport

    Annu. Rev. Biomed. Eng.

    (2004)
  • C.R. Ethier et al.

    Introductory Biomechanics: from Cells to Organisms

    (2007)
  • Y.C. Fung

    Biomechanics: Motion, Flow, Stress and Growth

    (1990)
  • Y.C. Fung

    Biomechanics: Mechanical Properties of Living Tissues

    (1993)
  • Girard, M.J.A., Downs, J.C., Burgoyne, C.F., Bottlang, M., Suh, J.-KF. Peripapillary and Posterior Scleral Mechanics,...
  • M. Girard et al.

    Age-related Alterations in the 3D, Nonlinear, Anisotropic Mechanical Properties of Non-human Primate (NHP) Posterior Sclera

    (2008)
  • M.J. Girard et al.

    Experimental surface strain mapping of porcine peripapillary sclera due to elevations of intraocular pressure

    J. Biomech. Eng.

    (2008)
  • M. Girard et al.

    Effects of storage time on the mechanical properties of rabbit peripapillary sclera after enucleation

    Curr. Eye Res.

    (2007)
  • P.R. Greene

    Closed-form ametropic pressure–volume and ocular rigidity solutions

    Am. J. Optom. Physiol. Opt.

    (1985)
  • A. Heijl et al.

    Reduction of intraocular pressure and glaucoma progression: results from the early manifest glaucoma trial

    Arch. Ophthalmol.

    (2002)
  • H. Huang et al.

    Cell mechanics and mechanotransduction: pathways, probes, and physiology

    Am. J. Physiol. Cell. Physiol.

    (2004)
  • J.D. Humphrey

    Cardiovascular Solid Mechanics: Cells, Tissues and Organs

    (2002)
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